Tumors, stenoses of biological conduits, and other proliferative lesions can be effectively treated with radiation, which is known to inhibit cellular proliferation. The mechanism by which radiation prevents such proliferative cellular response is by preventing replication and migration of cells and by inducing programmed cell death (apoptosis).
Cells are variably susceptible to radiation, dependent on the types of cells and their proliferative status. Rapidly proliferating cells are generally more radiation-sensitive, whereas quiescent cells are more radiation-tolerant. High doses of radiation can kill all functions of even quiescent cells. Lower levels can merely lead to division delays, but the desirable effect of reproductive death is still obtained. In this case, the cell remains structurally intact but has lost its ability to proliferate, or divide indefinitely. It appears that low level radiation produces this desirable effect without causing tissue destruction or wasting (atrophy).
Traditional high-dose external beam radiation treatment, and prolonged low-dose radiation treatment (brachytherapy), are well-established therapies for the treatment of cancer, a malignant form of cellular proliferation. In particular, attention is currently being directed to the practical aspects of the use of brachytherapy. These aspects are, of course, particularly significant when radioactivity is involved. A disease site in a patient may be exposed to radiation from an external beam, either as a stand-alone procedure or in conjunction with an operative procedure. Alternatively, the radioactivity may be incorporated into an implantable device. In the first case, higher intensities of radiation are needed. As a result, other organs may be unnecessarily exposed to radiation, and safety, handling and logistics problems arise. In the second case, the implantable devices are typically quite expensive. In particular, if radioactivity is added to the device, the device may only be effective for radiotherapy during a relatively short period during which the radioactivity is provided at a useful (therapeutic) level. Depending on the radioisotope used, the decay time may be as short as hours, days or weeks.
The current state of the art brachytherapy for treatment of localized lesions such as tumors of, for example, the prostate, breast, brain, eye, liver, or spleen, employs radioactive, "sealed source" seeds. The term "sealed source", as used herein, means that radioisotopes incorporated into a device are integral with the device and cannot be dislodged or released from the host material of the device in the environment of usage. A typical sealed source seed includes a radiation source encapsulated within an impermeable, biocompatible capsule made of, for example, titanium, which is designed to prevent any leaching or release of the radioisotope. The seeds are approximately the size of a grain of rice (typically 0.81 mm in diameter by 4.5 mm long) and are implanted individually at a treatment site within and/or around a lesion, typically with a medium bore (18-gauge) delivery needle.
Disadvantages of the use of such seeds as radiotherapy devices include their nature as discrete, or point, sources of radiation, and the corresponding discrete nature of the dosages which they provide. In order to provide an effective radiation dose over an elongated or wide target area, the seeds should be uniformly and relatively closely spaced. The need to ensure accurate and precise placement of numerous individual radiation sources undesirably prolongs the exposure of the surgical team to radiation. Moreover, the use of discrete seeds requires an elaborate grid matrix for their proper placement. This requirement is labor-intensive, and therefore costly. In addition, the discrete nature of the seeds renders them more susceptible to migration from their intended locations, thereby subjecting portions of the lesion, the treatment site, and surrounding healthy tissue to over- or under-dosage, reducing the effectiveness and reliability of the therapy.
Other disadvantages exist in radioactive seed therapy. Relatively few radionuclides are suitable for use in sealed-source seeds, because of limited availability of radioisotopes with the necessary combination of half-life, penetration depth and activity, and geometry. In addition, the implantation of seeds generally requires a delivery needle with a sufficiently large bore to accommodate the seeds and may, in some cases, require an additional tubular delivery device. The use of a relatively large delivery needle during seeding may cause unnecessary trauma to the patient and displacement of the lesion during the procedure. Also, because of the risk of migration or dislodgement of the seeds, there is the risk that healthy tissues near or remote from the lesion site will be exposed to radiation from seeds which have become dislodged from their intended locations and possibly carried from the body within urine or other fluids.
In an attempt to accomplish a more even distribution of radioactive seeds in a longitudinal, or z, direction, the so-called "rapid strand" approach provides a bioabsorbable strand or suture onto which several radioactive seeds have been preassembled in a uniform spacing approximately 10 mm apart. Unfortunately, although the seed spacing along the strand can provide a somewhat more uniform longitudinal radiation dosage to the patient, the strand itself may not be sufficiently rigid to allow it to be properly and reliably installed at the treatment site without becoming jammed in the delivery needles. In addition, because the dosage is administered from seeds, the radiation dose provided thereby has the limitations previously discussed relating to the discrete nature of the seeds.
In the treatment of intraocular tumors, hemispherical ophthalmic plaques incorporating a radioactive material are sewn directly to the eyeball to provide a radiation dose to the intraocular tumor on the concave side of the plaque. In one type of plaque, manufactured by Bebig (Germany), a thin film of Ru-106 is encapsulated within two sheets of silver. The silver sheet on the concave side of the plaque is approximately 0.1 mm thick, and the sheet on the convex side is approximately 0.7 mm thick. The plaque has a total thickness of about 1 millimeter. Greater sheet thickness provides additional radiation shielding but adds to the thickness of the plaque, which increases the discomfort to the patient.
In another embodiment, radioactive seeds are attached to the concave side of the plaque in a grooved polymer liner. However, because the radioactive seeds are themselves relatively bulky, these plaques are relatively bulky and therefore uncomfortable for the patient. In addition, nonuniform dose distribution appears to be unavoidable with plaques into which seeds are inserted. It is critical to provide a minimum dosage to every part of a tumor so that it can be eradicated without risk of redevelopment. On the other hand, a radiation source which is too energetic may penetrate beyond the intended treatment region and undesirably expose the optic nerve, the lens, the brain, and other radiation-sensitive tissues and organs to radiation. Certain radionuclides are disadvantageous because they inherently deliver an excessive radiation dose to the sclera. Other undesirable radiation sources may include higher-energy gamma rays which may penetrate deeply into the tissues surrounding the eye and also pose a risk of overexposure to the surgical team. It is therefore difficult to provide the appropriate dosage to the patient using currently available intraocular plaques.
U.S. Pat. Nos. 5,607,442, 5,059,166 and 5,176,617 to Fischell et al. disclose the use of radioactive stents for use in the treatment and inhibition of stenoses in biological conduits. Irradiation of biological conduits from the inside is known to prevent or inhibit cellular proliferation after injury or trauma, such as angioplasty and other surgical procedures, to the tissue. A radioisotope is integrated into the material of the stent by coating, alloying, or ion implantation methods.
The radioactive stents disclosed in the Fischell et al. patents are substantially tubular mesh structures which emit radiation in a generally cylindrical radiation pattern about the stent. The radiation pattern is thus defined by the entire geometry of the stent and not the specific application for which the stent is used.
One problem associated with the radioactive stents of Fischell et al. is the relatively inefficient, and somewhat indiscriminate, distribution of radioisotope over the surface of the device. The lattice structure of the Fischell et al. stents is believed to be uniformly coated or treated with a radioisotope in order to render the structure radioactive. The omnidirectional nature of radiation emitted from a radioisotope-treated mesh is relatively nonuniform in its intensity and distribution, primarily because of the mesh geometry of the device. Irradiation of a surface produces a radiation pattern which extends in a direction normal to each treated surface. If the surface is a lattice or mesh, radiation may be emitted in all directions from each treated crosspiece of the lattice. In many cases a significant amount of radiation emitted from the device, such as, for example, radiation emitted inwardly toward the central axis of the stent, or between adjacent crosspieces of the lattice, may be unusable, or even potentially harmful to surrounding tissue, because of its open mesh geometry.
It would be an advancement in the art to provide a general purpose radiotherapy delivery device which provides a selectively controllable dose of radiation in a predetermined and discriminating radiation pattern, without the risks of over- and under-dosage attendant with the use of radioactive seeds, or the problems associated with indiscriminate radioisotope distribution over the mesh structure of the type suggested by the Fischell et al. patents.